S2 E15 Science Under Siege: A conversation with Dr. Uğur Akcan and Dr. Dritan Agalliu about PANDAS Research, NIH Cuts, and the Power of Community

Episode Transcript
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Dr. Susan Manfull (00:07):
Untangling Pandas and Pans is a podcast
about two little-known medicaldisorders characterized by the
sudden and dramatic onset ofsymptoms such as obsessions and
compulsions, vocal or motor ticsand restricted eating behaviors
, and a whole host of othersymptoms following a strep or
other bacterial or viralinfection.

(00:29):
I have the privilege ofinterviewing some of the top
researchers and clinicians inthis rapidly growing area, known
by various names such asimmune-mediated neuropsychiatric
disorders, infection-associatedneuroimmune disorders and
autoimmune encephalitis, orsimply PANDAS and PANS.
My name is Dr Susan Manful.

(00:50):
I am a social psychologist, theexecutive director of the Alex
Manful Fund and the mother ofAlex Manful, who died at 26
years old due to PANDAS, adisorder my husband and I knew
next to nothing about, certainlynot that our daughter could die
from it.

William Manfull (01:18):
This is episode 15 of Untangling Pandas and
Pans, recorded June 28, 2025.

Hello everyone, welcome to the 15th
episode of Untangling Pandas andPans, a podcast hosted by the
Alex Manful Fund.
I am Susan Manful and today Ihave the pleasure of welcoming
Dr Ur Akcan.
Dr Akcan is a postdoctoralneuroscience researcher at

(01:50):
Columbia University and Dr JatanAgalew's lab, all in New York
City.
Sadly speaking, his work is inneuroscience, as I mentioned,
where he's had a long interestin the development of
neuropsychiatric disease,particularly the role of the

(02:13):
immune system in the developmentof disease.
We'll talk about some of theinitial questions that intrigued
him at the very beginning ofhis career, such as, very simply
, what is the influence ofpsychological stress on the body
?
Does it trigger an inflammatoryresponse, an abnormal immune

(02:35):
signal that plays a role in thedevelopment of disease?
His curiosity, as well as theopportunities that popped up
during his career, led him tohave a strong interest in the
role of the blood-brain barrierin disease, both in terms of the
delivery of drugs to treatdisease and in the development

(02:59):
of disease.
All along, he viewed the bodyas a system.
Everything is connected.
The individual parts talk toeach other, so to speak, and in
terms of neuropsychiatricdisorders, the immune system
plays a huge role in connectingthe body and the mind or the

(03:19):
peripheral nervous system, andthe brain.
The blood brain barrier was anatural area to focus on.
Dr Akcan hails from Istanbul,turkey, where he also completed
his master's degree and his PhDhis dissertation before COVID,
during which time he alsomanaged to do some research on

(03:41):
COVID.
To do some research on COVIDand after COVID he came to the
States to work with Dr Agalu.
He was working, generallyspeaking, with Dr Agalu on how
repeated group A streptococcusinfections trigger the immune
system or trigger immune systemresponses that affect brain

(04:04):
function, leading to disorderslike PANDAS and Sydenham's
chorea.
His work explores the role ofthe immune system, both adaptive
and innate, and its impact onneuropsychiatric symptoms,
especially obsessive, compulsivebehaviors.

(04:25):
He was awarded a veryprestigious two-year
postdoctoral fellowship thatbegan in September 2024.
And six months into it, whileimmersed in some very exciting
research in genetics and pandasand pans and in the role of th17

(04:49):
, funding for this fellowshipwas suddenly, with no notice,
terminated, along with 400million dollars of other funding
at Columbia.
So, just briefly, why did thishappen?
Let me just say that the Trumpadministration claimed that the

(05:13):
protests on campus againstIsrael's military campaign in
Gaza were anti-Semitic andtherefore terminated the funding
until the university made alist of policy changes focusing
on rules for protests, wearingface masks during protests and

(05:35):
reforming its Middle EasternStudies Department.
The Trump administrationthreatened that the university
could lose more funding unlessthese changes were made.
The university capitulated and,as I understand it, though,
columbia has still not receivedthe funds that were terminated

(05:57):
back in March, and we'll talk alittle bit more about that with
Dr Agaliu at the end of myconversation with Dr Ak-Chon.
This situation, as listenerswill hear at the end of our
interview from Dr Agaliu, wasdescribed by him as absolutely

(06:22):
devastating in every realm Foryou, dr Ak-Chung and your family
, and for the research, butfortunately, thanks to the
efforts of Dr Agaliou, who begana GoFundMe campaign, he was
able to thus far save your job,your postdoc funding and the

(06:45):
research, and you've been ableto stay and you're here today
talking with me.
Dr Agaliu will talk about thisfund and the generous
contributions from manyindividuals, as well as
nonprofit organizations,including the Alex Manful Fund,
pandas Physicians Network,pandas Network, northwest PANDAS

(07:07):
, PANS Network and the LookFoundation.
Fortunately, because of theefforts of everyone, you are
still in the Agaleo Lab and I,as well as many other people,
would like to know more aboutyou and your research.
So let's begin with your viewsabout, just generally speaking,

(07:34):
about neuroinflammation andpsychiatric disorders, which is
where you started, and we canwork our way into hearing your
master's research, yourdissertation for your PhD, and
continue on to present day.
So again, welcome, dr Akcan,and let's get started.

Uğur Akcan, PhD (07:59):
First of all, thank you.
Thank you for all of your helpto our works and also all the
people and all the foundationsupport has to continue this or
studies.
And then also I need to includethat your pronunciation of my
last name one of the best that Iheard and I'm really happy to

(08:21):
hear that, because it was a longtime to hear my last
improvisation that correctly.

Thank you for that.
Thank you for that, but I doconfess I practiced.

Still, it's amazing.
Just take your time, thank youso much.
And then you made a goodintroduction for me and then you
started with the question how Iinvolved or how I start, what
is the important thing for me?
And then you start with thequestion how I involve or how I
start, how, what is theimportant thing for me?
Uh, before, during, actuallyduring my bachelor degree, I
studied the biology and I wasinterested the brain part, so

(08:56):
how we are thinking, what is thesteps for thinking, or what is
the affects the thinking processor what is the effect or
behaviors.
So I start, I would like toinvestigate this question.
But after that I realized thatthere is something that should
affect the thinking or thebehavior, not from the central
nervous system.
There should be some cues inthe peripherally affects the

(09:21):
central nervous system orthinking or behaviors.
And then it's kind ofinteresting question.
And then it's kind ofconsidered, as the brain is the
immune privilege organ and thebrain is the, you know, the
special central nervous systemis restricted from the body.
There is no cues that can enterthe body.

(09:41):
But after the time passedpassed, people started to
recognize that also brain has uhaffected by the peripheral
immune system or the otherorgans too, because brain needs
to govern these organs, right?
So I?
And then this is how I startedI I started asking question this
one what will stress?
Because we know that thesebehavioral changes can affect,

(10:06):
can cause some stress.
Can we detect this one in theperipheral organs, such as blood
?
And then I started asking thisquestion in my master degree on
the bipolar disorder patient.
If someone does not know whatis the bipolar disorder, it's a
behavioral disease that affectsthe people, mood in long term.

(10:27):
The people who are diagnosedwith the bipolar disorder has
some mood episodes.
They switch between depression,the mania which is you can call
they are hyperactive, they aremore tend to be gambling, they
can risk everything and thenthey lose their judgment.
Or some of the patients do notreach this mania level, they

(10:50):
just stay just a little below ofthe mania.
But they can stay.
And I was really interestedbecause I was like, okay, there
is some time and then duringthis time the people mind or
behavioral can switch betweendepression to mania phase and
then they can be stable, theycan live their life in all year

(11:12):
just as the normal people, andthen they can switch and we
never know that.
And then I was lucky enough towork in the medical center in
Istanbul and then it's one ofthe biggest one.
So I started asking thisquestion what will happen if we
can capture the people who hasthe first episode, actually
first diagnosed episodes intheir life versus the chronic

(11:35):
bipolar disorder patient?
Chronic means that if thepeople have more than two
episodes, we consider them as achronic bipolar disorder.
So I would like to ask thisquestion Okay, the first time of
the stress versus the multipletime of the stress can cause

(11:57):
some alternation in immunesystem?
I would like to ask thisquestion because during the time
that I'm working on this one,there are also lots of studies
for focusing on that.
In schizophrenia or depressionthere are some immune activities
.
So I just tried, I just copied,because I I was in the master
and was very young, you know so,but we did, we just try to

(12:21):
collect the blood sample of thepatients and then we try those
diagnosed with bipolar.
Yes, as well as the controlcases, because we should have
the bases and then we lookthrough what is the changes on
the complement system.
I need to also define what isthe complement system.
Complement system is one of themain part of the in-nut immune

(12:43):
system.
It helps to recognize thepathogen and then destroy the
pathogens.
And then having more complementsystem means that there is some
immune activation occurs andalso there is some infection or
infection related activationstriggered in the human body.
So I would like to examinethose pathway.

(13:05):
I investigate those complementsystem elements in this patient,
as well as the control cases.
After I mentioned thecomplement system, I need to
also tell that during my thesisprocess there is one good study
coming from the United States.
They investigate theschizophrenia cases and then
they look through the.
They investigate theschizophrenia cases and then

(13:26):
they look through the.
What is the mutation in thisschizophrenia patient?
And one thing that they foundis that C4, which is one of the
important elements of thecomplement system, has a
mutation, and then they foundthat the mutation in the C4
might have correlation with thedevelopment of the schizophrenia

(13:47):
in some patient.
So I was very excited after Iread this one and I was like,
yeah, maybe I I'm in the goodyou know track.
So what we found is that thereis a clear differences between
the chronic phase versus the thefirst episode.
And then the complement systemis way more depleted in the
serum in the chronic phase.

(14:09):
So, and then first episodefound that it's very elevated
and the mRNA levels I mean thatthe DNA expression levels of
this complement system isbecoming up in the chronic stage
.
So what we think?
That after our finding maybethis chronic case, they have a
huge stress and a serumcomplement elements are depleted

(14:30):
and then they started toreplace it back.
But in the first time, in thefirst episode one it's very new
for them they are activatingtheir stress response and then
they just try to fight withsomething.

I think that your research underscores the
importance of identifyingpsychiatric disorders early on.
We know that with schizophrenia, that it's very important to
focus on these first episodeschizophrenic cases, because

(15:05):
they're much more easily treatedthan the chronic cases, and so
your initial research wouldsuggest that that may well be
the case for bipolar yeah, itmight be.

It might be.
Yeah, you're right about it.
And also, uh, I need tohighlight this one it's kind of
quilting, that showing that wedo not know yet Is it started
from the periphery or is itstarted from the central nervous
system.
It is out of scope of my work,but we know one thing sure,
there is something affecting theimmune system, or there are

(15:41):
some pathways that affecting thewhole body, or there are some
pathways that are affecting thewhole body.
So it's kind of a good way tostart my career to finding this
one, because, as you mentioned,I'm always interested in how the
body reacts against thebehavioral changes, or how the
body can cause changes in yourbehavior.

(16:01):
So it just helps me to find asmall path at the very beginning
to work on it.

And so the trigger could be external, in
the case of, say, infection, orit could be internal, as in the
case of, say, metabolic issuesin the body, much like PANS and
PANS.

Both could be true.
For example, maybe we are goingto talk about my recent study,
which could be one of theanswers to your question.
So we can say it like thisMaybe the common infection might
cause this development ofdisease not for all the cases,
some of the cases and then therecould be some mutations.

(16:51):
It could be external stimuli,it could be internal mutation,
metabolites and also as well asthe immune system.
Maybe we can say that there issomething in the neurons which
affect our body, so our body tryto compensate the this abrupt

(17:12):
or disturbed signal coming fromthe neurons.
So we need to think also thisway too, because my I need to
highlight this one my firststudy doesn't give any answer
about this one.
We just try to read theoutcomes.
We do not try to eliminate thecauses.

Mm-hmm.
Oh, it's just early research,but it got you, fortunately,
into this area and with your PhDyou moved into a different area
, related of course, but adifferent one.
Can you tell us a little bitabout that transition from

(17:55):
understanding neuropsychiatricdisorders to the blood-brain
barrier?

Yeah, maybe you'll notice that I'm really
interested in working on thedisorders.
And then, after nearly endingmy master thesis, my PhD advisor
found me and said oh, you knowwhat?
There is something that'scalled the blood-brain barrier
which blocks to treating someneurological disorders such as

(18:25):
Alzheimer, parkinson.
I need to give this example.
Normally lack of dopamine isParkinson disease patient, so we
need to give them the dopamine,right?
It's pretty easy question.
If they lack of dopamine, let'sgive them dopamine.
But unfortunate thing is thatthe blood-burning barrier

(18:45):
restricts the penetration ofdopamine into the central
nervous system.
So it's a major challenge.
And then maybe in some cases,for example in the
neuropsychiatric disorders,people find that, oh, we find
some drug, it helps, it can cure.
But when we turn this one intothe clinical studies, it is not

(19:05):
working.
Why?
Because it cannot pass throughthe blood-brain barrier.
Blood-brain barrier, it's kindof the vascular system.
And then this vascular systemis specified for the central
nervous system and then theendothelial cells of this
vascular system, especially inthe capillaries, has barriers.

(19:26):
They tightly seal with eachother and then not any molecule
can easily pass through betweenthe two cells.
It's very tightly sealed.
And then also these cells havethe pumps and then when
something enters in their cell,and then they just pump back and
if they do not like it, theywill like okay, you will go to
the blood side again, not to thecentral nervous system, sir.

(19:49):
You need to go to the flow andthen.
But this endothelial cellsalways let the penetrate, for
example, important moleculessuch as glucose, the oxygen,
water, into the central nervoussystem.
So my phd advisor told me thatoh, this is the case.
And then I know that you wouldlike to work on the diseases.

(20:10):
So what do you want to work onthis field?
And I try to find a way how wecan improve the delivery of the
drugs into the nervous systemfor this patient or these
disease cases.
And then my PhD thesis ismainly working on the
development tools, such asnanoparticles, to send these

(20:34):
drugs into the nervous system.
And most of our cases, likesepsis and epilepsy these are
the diseases that are mostlyimportant because, for example,
some of the epilepsy casescannot be treated.
We do not know yet.
Some of the researchers believethat these drugs cannot

(20:56):
penetrate enough, so the nervoussystem treats these patients.
So what we try to do?
We try to conjugate our drugswith the nanoparticles and then
try to send them into thecentral nervous system.
And my thesis was is the kindof different than what we
generally do.
I try to find a possible entryroute for the drugs into the

(21:19):
brain.
I use the histamine, which is avery biological molecule.
You everyone has the histamine.
But what we know that histamineis important for the allergic
reaction.
It's important for theregulation your sleep and also
as well as your behavior.
But one good, cool thing abouthistamine we know that histamine

(21:41):
can open the blood-brainbarrier.
If you apply the histamine inhigh level above than the normal
levels of the histamine, weknow that it's affect the
vascular permeability in theblood-brain barrier.
So I try to find a opening wayand reclose, because when I give
my talk everyone's like, okay,let's open, but it's not good

(22:05):
because we need to re-close.
We need to re-seal Because ifyou let the entry of all things
into the brain, brain will bedamaged.
That's why we have the barrierat the very beginning, because
the central nervous system pH isdifferent than blood, the water
level is different, theelectrolyte level is different

(22:28):
and it's a very strictrequirement to proper working.
So my thesis I need to find away, open and close it again.
So I thought I can use thehistamine, because histamine has
four different receptors.
And then we try to alsounderstand that which receptor
is important for the blood-brainbarrier, especially in the tail

(22:50):
cells.
For that reason we try to usehistamine.
Then we try to use thehistamine receptor inhibitors
specifically, and then what wefound is that the histamine
receptor 3 is could be.
And then what we found is thatthe histamine receptor 3 could
be prophylactic, which isimportant, which most of the

(23:12):
people use this histaminereceptor 3 inhibitor for their
allergic reaction inhibitors.
I cannot tell the drug name inhere because in Turkey they are
different.
I know that.

But something like Benadryl.

Yeah, most of the sproxifen or this kind of
drugs that most of the peopleuse for the treat their allergy.
We know that it's important andwe saw that it could be
important.
But I need to also highlightthis one we need to do a major
study because histamine has arole of the various biological
sources.
So that's how I moved to PhD.

(23:44):
That's how I followed my PhDthesis, actually.

So thus far, we can see your interest in
understanding psychiatricdisorders and understanding the
role of the immune system thataffects both the peripheral
system and the brain or thecentral nervous system,

(24:11):
something that was not accepteduntil recently that the brain
does have its own immune system,and we can see your your
interest in well, drug deliveryand and I think that that set a

(24:31):
great stage for your interest inworking in Dr Agalu's lab,
because all of those componentsare there, plus another one that
you didn't really elaborate onbut I know it's one of your
interests so why is it thatcertain people develop those

(24:54):
disorders?
Not everybody who gets strapped,of course, has pandas, so
that's also another one of yourinterests.
But before we get to Dr Agalu'slab, covid came along into Dr
Agalu's lab.
Covid came along and toillustrate what a prolific

(25:18):
researcher you are, you managedto get together with a group of
other researchers and conduct astudy during that time, during
the lockdown.
Can you just tell us just alittle bit about that work,
because of course I think thatmay come back and intertwine

(25:38):
with your current interests,even.

Yeah, first of all, thank you again.
But I need to clear one thing.
We started this study with justtwo of my friends.
All of us were PhD students.
We've been in, you know, wehave been in the lockdown.
We are just stayed at our homeand then we make these Zoom
calls.
You know, it was very famousthat day and we started to make

(26:04):
a Zoom call.
And then I have my baby.
My baby was four months old.
We just started talking witheach other every day and then we
were like we need to dosomething.
Guys, we know something.
For example, I know blood-brainbarrier, and then I know the
physiology of the human body orthe animal body.
And then one of my friends isthat it's knows how to make
recombinant proteins.

(26:25):
Other friends know how cellswork.
So we just started giving theideas, throwing the ideas with
each other.
We just talking, talking andthen at the one point we just
couldn't stop themselves.
And then we send an email touniversity board.
Hey look, I know there are someresearchers that you assigned
to work on this case, but we arejust three phd students.

(26:45):
We would like to do something.
And then, thanks to ouruniversity board, and uh or pis,
they just told us that go,please, do whatever you would
like to do.
And then this is how the studystarts, actually, because I'm
always would like to tell thisstory.
If you just want to dosomething, start doing something

(27:08):
and then tell the people, suchas because people will help you,
such as you right now, you arehelping us and then we starting
to do jobs is.
Our idea is that we know thatthe SARS-CoV-2, this virus,
requires the h2 for entry intothe cells.

(27:28):
So we try to do into the cells.
So we try to do.
We try to make new recombinantproteins contain lots of H2.
So this protein, therecombinant protein, can bind to
the old recombinant H2 and thencan envelop the virus and the
virus cannot enter the cells.
So we just designed this proteinand then we isolate this one

(27:52):
and then we test it in the cellsand we test this in the animal.
Our results shows that it couldbe useful, but during this time
people already managed to findthe viral vaccines against it.
But it stayed there At least.
It's kind of one of theimportant stuff that I've been,

(28:14):
I've ever done, because it'scompletely our study with my
friends.
We are still talking with them,we are making podcasts with
them in my own native languageand then just showing that
showed us, showed me, that ifyou just would like to do
something, just do your best and, as someone who will recognize
after this recognition, you cando whatever you would like to do

(28:36):
.

Very interesting and I just think
that you illustrate twoqualities that I think are so
important in researchers andclinicians and that is curiosity
Definitely researchers andclinicians.
And that is curiosity,Definitely Curiosity Whoever
curiosity can drive those peopleI want to work with and

(29:02):
perseverance.

If you don't get it the first time around,
keep going.
No lie, I need to tell onething after you say that we
write like a four or three orfour different projects and when
we started we just we wouldlike to do something against
this disease.
We just think that we areresearcher, we are scientists,
we need to sign step up becausewe know something that normal

(29:30):
people maybe do not know, or wejust spend our life to give some
answers.
So this is how we started andthen we made three failures,
three or four, and then rightnow we are there perseverance,
perseverance, that's great.

So tell us what took you to Dr Agalou's lab
.

I need to also tell this one In the science,
there is one thing common Afteryou finish your PhD, you need to
move your lab from thedifferent lab.
This is the common ruleunwritten rules for the science
because you need to move, carryyour knowledge from your

(30:26):
previous lab or whatever you didbefore, to new lab that you're
going to attend and you need togather the knowledge from them.
And then you need to createyour unique working ideas or
projects, or the ideas to puttogether.
This is the common thing forscientists.
So after I finished my PhD, Itried to follow this rule.

(30:48):
Luckily I followed.
I tried to follow this rule.
Luckily I followed.
But before this rule, I createdshort leads for me, the PIs that
I would like to work, andDrittan was one of the top of it
.
But I was really scared becausehe's just kind of a very
profilic guy.
He knows blood-brain barrierand then he knows he works on
the neuropsychiatric disorders.

(31:08):
So it's kind of a goodcombination, but unfortunately
there was a covid, so I justreally, you know, uh, hesitant
to send in.
Send an email.
So I send an email.
Say that, hey, dr agali, I'mirakcan from the you know, the
turkey, and this is my job, butI would like to explore the

(31:32):
possible working opportunity inyour lab.
Luckily, he returned me and Isaid, yeah, you know what, I
have one openings.
And then he mentioned theproject that he did and then,
during this time, he mentionedthat some disease called the
pandas, which I wasn't aware ofwhen I was in Turkey.

Let me stop you right there, just to make
sure I understand that you didnot know anything about pandas
and pans before you came to thiscountry and worked in Ceytan's
lab.
That's very interesting.

Yeah, I need to tell this one.
I was aware that someencephalitis might cause the
behavior abnormalities, but Iwasn't aware that there is some
sort, some group of children whocan develop and then it caused
this big problems for families,children and, you know, everyone
community.

(32:24):
I wasn't aware that there is aspecific disease called as a
pandas or pans.

Interestingly , pandas and pans are really at
the intersection of all of yourinterests.

Yeah, and the funny thing is that when Drita
mentioned about this job, I waslike, yeah, I can work in it,
and I turned my.
You know, after that I need totalk with my wife.
Hey, you know what?
We are going to America and Iwork in this project.
And she was like she needs tohear this.
And I was like you know what?
We are going to America and Iwork in this project.
And she was like she needs tohear this and I was like you
know what this project contains?
Everything that I would like towork.
She was like, well,neuropsychiatric disorders,

(32:59):
blood burden barriers and immuneactivity.
Exactly, I just jumped on thetrain and then he mentioned that
because after our conversation,right after that, I started
working on this.
When I was working on this, Iwas like, okay, I got it,
because it's infection.
There's a definitiveinteraction with infection

(33:22):
versus the behavioralabnormalities.
This is the one thing that Iwould like to always work.
Peripheral things can causesome change in the brain and
then it's effect our behaviorsand that goes back to your, your
master's thesis yes, and I cantouch base the blood-brain
barrier too very interesting howthese things turn out in life

(33:47):
yeah, I'm surprised, I'm just uh, it's kind of it might be heard
that it's spiritual, but Ialways believe that if you want
something too much and then ifyou not stop yourself to working
on this I'm not saying thatworking just continue to do
whatever you like to do.
Life will give you theopportunity to work on whatever

(34:07):
you would like to.
At least you will have onechance to show yourself or test
yourself on your dream path orthe path that you would like to.
At least you will have onechance to show yourself or test
yourself on the your dream pathor the path that you would like
to be in well, that certainlyhappened here.

And to think that you were nearly booted out
of this position.
The funding was terminated andyou nearly had to to leave, but
fortunately you didn't.
So give us an idea of whatyou're doing now and you can
start off with the RXRA geneticsresearch if you'd like, or the

(34:42):
TH17, or whatever you prefer.

Yeah, before I joined the lab, there are some
studies already conducted andone thing that the return showed
, which is I will be part ofthis study too and then
transcriptomics.
This shows that in the brainafter the infection, microglia
are the main cells that, uh,showing the alternation after

(35:06):
the infection and tell us whatmicroglia are they are are
actually one of theimmune-resistant cells of the
brain.
It helps to regulate the immunefunction, for example neural
clearance, sensing theabnormalities and then giving
response against it.

(35:26):
So the microglia is working oncontrolling to the the brain
homeostasis.
And then what we found is thatthese macroglias showing high
changes after the infection.
And then there is also so manystudies show that the macroglial

(35:49):
abnormalities can causeneurobehavioral changes.
So we just, Diritan and his lab, found this one before I joined
.
And then my story started afterthis one, because we would like
to understand why some of thecases are vulnerable against the

(36:12):
streptococcal infection,because it's very common, it is
can it can happen to everyone,but why some?
Some patients develop this one,others not.
And then for understanding thisone, we collected the human
patient samples, that actuallysamples from the pandas and cdm
core, and then we made the wholeexome sequencing and then we

(36:35):
found that the RX-RA, which isabbreviation of the retinic
receptor X-alpha, has mutation.
It's common for these cases.
And then what does that mean?
That if you have this mutationyou might be under the risk of

(36:56):
the develop pandas.
That's our finding.
And then right now I would liketo explain what is the RxRA,
what is the role of the RxRA andwhy we decided to use the RxRA
orUS RxRA?
Because there are other genesthat we found that has a
possible mutation.
Rxra is a transcription factor,which is what is the

(37:21):
transcription factor?
Transcription factor is theproteins or the factors that
governs the other proteinexpressions, that governs the
other protein expressions.
So what does that mean?
That this transcription factoractivation or inhibition will
cause the protein expressionchanges.
So that's the reason why wecall it the transcription factor

(37:45):
.
It's important for the otherprotein's expression and there
are some studies that conductedon the rxra, which is showing
that it's main expressed in themyeloid cells and also t cells,
the.
I need to open the myeloidcells, macroglia and macrophages

(38:06):
.
That's why I started the, mytalk with the.
What the found at the endreturn lab found at the very
beginning.
We found that the microgliashowing the huge variation.
So that's why we was like, okay, there is something that could
be interesting.
And then when we look at thefunction of direct x-ray, it's

(38:26):
important for the infection andalso the lipid metabolism, which
two pathways are important.
You know could be important forour case, because you know that
there is strep infection, countthis one for PANDAS cases and
also maybe the other lipidpathways involved.
So that's why we choose the Rxarray.
Actually, After that we gatherall findings and or we we

(38:55):
thinking this one let's checkrole on RxRA of the disease
development.
Maybe some of you know that inour lab we have very well
working animal model.
We can mimic what is happeningto this pandas or panth child in
our mice model.

(39:15):
Working on the mice model, veryhelpful because we can
specifically remove or interestthe gene in or desired cell type
.
So we just think that let's tryto remove the rxra gene from
the oil or microglia and thencheck what's changing.

(39:38):
And then we did this similarexperimental model that we did
before.
And then we infect this animalwith the streptococcus five
times and then we look through,look their brain or analysis
shows that absence of the microrx array from the microglia
after the infection cause lessimmune response.

(40:01):
So that's mean that thismicroglia cannot generate enough
immune response to regulatebehavioral or neuronal changes
after the infection.
So it is important becausewe're thinking that without
Rx-ray your microglia is notworking properly and then it's

(40:21):
just aligned with the oldgenetic study.
So it's kind of a good hit.
We found that this gene could beimportant, might cause the
underlying risk of thisdevelopment of disease.
And then all animal models showthat yes, because their
microglia might not be workingproperly.

(40:42):
So their microglia are actuallynot capable of generating exact
immune response against thisinfection.
So maybe this is why some ofthe child are under the risk.
It is important having the Th17cells, because these cells
actually one of the maincomponents of the immune cells.

(41:03):
And then what we know in that,what we know that in this
immunological reaction, thesecells, if it's happening in the
central nervous system, in brain, I mean they can move towards
the brain and then in theregular context they're helping
your body, but in the diseasecontext they're not helping your
body.
But in our RxR case it is just.

(41:24):
I need to highlight this one.
It is too early to say mysentence, but I just want to try
to generalize our hypothesis.
Maybe these TH17 cellspenetrate into the brain and try
to activate the macroglia,saying that look, dude, we have
something in the periphery, andthen you need to help us to

(41:48):
control the brain, because weknow that brain is kind of
privileged organ and then maybemicroglia are not sensing.
Microglia are responsive.
Against this one, I need to dosome.
Uh, I need to validate mysentence to with after doing
some experimental analyzing butor results right now showing

(42:08):
this one so the th17 cells?

of course we do need them, but in excess they
are problematic.
Is that correct?

yes, okay, right now we know that there are
some love, there are some th7cells in the brain in the normal
context.
But if this number increase inthe normal context, but if this
number increase, if the if theseth17 cells are activated, it is

(42:42):
problem.
For example, the multiplesclerosis, your immune cells
penetrate into brain and thenthey are active and they are
starting to meal in of the mealin sheet that covers the neurons
, which is important for thefunctioning of the neurons, and
and then you have this kind ofdisease output, depending on
where your Th17 cells entry.
You're right about it.

Okay, All right.
So we know the Th17 cells arein the case of an infection and
certain people may be excessivein number.
Yes, or what have you?
And you know the role of the RxRa when not present, when the

(43:23):
genes are not there, that themicroglia can't work.

Yes.

Okay.
So we know those two things arehappening, but we don't know
exactly what that, how they'reconnected and what that might
mean.
But we do know it's an it's anabnormal situation definitely,
yeah, definitely, we show that.

Uh, it will be published soon.
I hope yeah, you're correctabout it because we know that
th17 cell numbers are increasedin this animal model.
So, we need to decrease this one.
But, as you said, we th17 cellsare macro.
They talk with each other.
Okay, maybe, for example, thein the peripheral system working

(44:18):
fine, and then they need totalk with the brain.
Guys, we have problem becausesome neurons are responsible for
the, you know, the regulatingthe body activities, and they
need to send some signals tothese neurons.
Maybe, guys we have problem,just send something, or help us
and signal, release thecholesterol, some stress

(44:38):
molecules, so we can fightagainst it.
And then maybe the paraphilicresponse is okay, but the
macroglia, which is importantfor the sensing, they lose the
ability of sensing.
They think that, oh,everything's fine, yeah, sunny,
yeah, there is no cloud.
And then, hola, because thereis an accumulated response

(44:59):
coming from the peripheralsystem, for example, th cells
just think about it th, some ofthese.
I'll say that, okay, they arenot talking, so let's go, let's
go.
I I'm sorry to explain that way, but because I have five years
old and then he asked me whatyou are doing, that I was like.
I try to give this kind ofexamples to explain what I'm

(45:19):
doing, just kind of by affectedwith five years old kids
questions.

Well, I actually like those kinds of
answers.
This is not my field, or atleast it wasn't my chosen field.

I think that this is also particularly
interesting because historically, uh, the microglia were not
thought to be very important inthe brain until recent years
yeah, especially I need to saythat it's became important after

(45:54):
the some finding the Alzheimerand Parkinson disease, actually
dementia studies showing that,because they found that the
microglia are not waste theclearance of, they're not
working properly to clear theamyloid beta in Alzheimer cases.
And then after these smallfindings, you know the small
stones becomes big stones, bigstone becomes.

(46:15):
You know the problems and thenpeople started sensing that the
microglia could be importantregulator and then, which is
true for actually all pandascases, so after the finding,
because microglia even cells sothat's how I start, actually how
the people starting to sensingthis one, because it's kind of

(46:37):
cells that everyone knows that-yeah it's a role, but right now,
everyone focus on the microgliabecause we know that there is
other studies showing that, forexample, microglia is important
for neuronal cell death.
It regulates the neuronal cell.
That people, after this findingpeople just say that, okay,
let's deeply focus on themicroglia.

(46:59):
Thanks to them.
So right, now we are in theposition.
We can work on the, we can usetheir findings in our studies
and then saying that, oh, look,that's the case for us or that's
not the case for us.
We can compare and contrast,try to find which parts are
unique for our cases.

So interesting how things change
over time.
So you're doing a lot ofresearch in this area and you
also have an interest inbuilding or creating a
blood-brain barrier model, a 3Dmodel.
Can you talk to us a little bitabout that and the importance

(47:41):
of that?

Yeah, I didn't give up my blood-brain barrier
career.
I'm just carrying this one withme and then.
I tried to implement myknowledge on the blood bed and
bearing in this study too,because we know that these
immune cells can penetrate intothe brain from the pedophilic
organs and then or previousresults show that the blood
barrier is not functioning inthe or animal model.

(48:05):
There are some permeability.
So we also need to figure thatout too, because if we can
return the blood-brain barrierin normal condition, maybe we
can also help patient.
But there are some limitationsto working on the blood-brain
barrier, which I didn't mentionduring my PhD thesis.
Animal studies you can do it,but you cannot manipulate how

(48:27):
much as you would like tomanipulate.
So for that reason we try todevelop the in vitro model.
In vitro means that thecellular model we just use the
cell-based system, which is,it's easy, doable and you can
test so many subjects in one day.
In animal it's hard becausejust think about it if you found
10 different tracks, that meansyou need to use hundreds, 200

(48:49):
animals to verify your findings.
But in this case I can use justone plate which consists of 100
cellular BBB models.
I just want to tell you whyit's important to have a
blood-brain-brain model, so 3D,because we know that these cells
should need to generate thecapillary structure they need to

(49:11):
form a tube.
Without tubes, what we know isthese cells do not functioning
as they functioned before.
So also, I tried to do this 3Dmodel, try to make capillary in
vitro cells and I'm using theother cells to test this one.
For example, in this rx-raystudy we would like to introduce

(49:33):
the ipsc derived microglia,which is stem cell derived
microglia, and then introducethe system to with or without to
having the rx-ray mutation tocheck that how this microglia
respond, because we would liketo understand that whatever
we're finding from the animalsis it true for human too.
It's also important becauseright now everyone works on the

(49:58):
mice.
Yes, it gives us so manyinformation, but mice is mice,
human is human.
We have similarities.
We have also differentresponses against this one.
So that's why we think thatmaking this model is important
Right now.
Actually, we can say that wecan create the capillary in the

(50:19):
flask and then we can testwhatever we would like to do.
So I created this 3D model.
Right now we are capable ofdoing this model.
And then our question was likethis one If this patient has
infection infection, so in theirsera they should have more
cytokine than average or thenormal human, normal condition

(50:42):
in the peripheral system.
Yeah, yes, yes, we justcollected the sera from the
patient and then we apply thissera in towards 3d system as
well as the control.
And then, because our idea waslike that, if there is an
infection, which which which isknown that it's effectively bb

(51:03):
permeability, and then weapplied, and then we found that
that the patient sera shoulddisplay high permeability.
So what does that mean?
This patient has some infectionand then this infection opens
the blood-brain barrier.
Maybe it's another contributionof why this patient developed

(51:23):
these behavioral changes.

So the infection caused the blood-brain
barrier to be more permeable.

Infection activates the immune system.
Immune system release somecytokines or chemokines which
can affect the blood-brainbarrier permeability, and then
it increased the BBBpermeability.

And is that in all individuals, or just
certain individuals that may bemore likely to develop something
like PANDAS?

believe it is true, actually it's true for
everyone.
But what I believe is that itcould be more important for the,
the pandas patient, becausethere are some things that they
develop right compared to thecontrol cases.
So I think this could be thecase.
They might have somethingunusual or maybe they are more

(52:16):
vulnerable compared to theothers.
So I need to tell one thingabout the cytokines levels,
because there is one recentstudy that highlights cytokines
could be important for theneuronal functioning.
I just want to say this oneSome basal levels of cytokine
required for the functioning ofthe brain.

(52:39):
So they focus on theinterleukin-17a, which is
important for TH17, which isalso important for our PANDAS,
because we show that TH17 cellsare important for the
development of this disease.
Pandas, because we showed thatTh17 cells are important for the
development of this disease.
What they found is that some ofthe neurons, which is important
for regulating the behavior,express interleukin-17A

(53:02):
receptors, so this neuron cangenerate response against the
cytokine.
And also there are so manystudies showing that the
TNF-alpha, theinterleukin-1-beta, also work as
a neurotransmitter for theneurons.
So why I talk too much?
Because I would like to say thatbody, actually brain, requires

(53:27):
some levels of the cytokines andchemokines, but it should be
strictly regulated.
If you increase the level ofthe cytokine and chemokine in
the brain, you will cause somechanges.
That's why I give you thisbrief information.
So in these cases, after theinfection, if you break down the

(53:51):
blood-brain barrier, there willbe more cytokine, there will be
more cytokine, there will bemore chemokine, so there will be
more immune cells.
So it is more than that thebrain can handle with the help
of microglia or with the othercell types.
So that's why it's important weneed to keep everything in the

(54:14):
in the homeostasis.
I mean the blood-brain barrierintact, the normal levels of the
cytokine.

Okay, and so the microglia play a role then
in in trying to decrease thenumber of TH17 cells under
normal circumstances.

Oh, maybe it's worked like that, just it's talk
with each other, and then th17cells could be told that, oh, I
just accidentally come here,show me how I can go back.
Yeah, and then but in this case, cases just think about it
these th17 cells are active,they are, they're just coming
from the war against theinfection.
After they they do not knowwhere they are and they talk
with the micro say that we arein the war, let's talk.

(54:54):
And then micro was like yeah, Isaw some cytokines showing me
that there are something goingon, more than usual, because
more than usual means that thereare some problems, and the
microglia became, you know,starting to create a response.
And then, after the showing theth70 cells, it was like yeah,
there is something going on,let's kill these neurons ah,

(55:15):
okay, that's the healthy braintissue that they're attacking.

That's the autoimmune aspect yeah, yeah,
actually oh, that's really sointeresting.
So a question that people likeme always have is is why the
basal ganglia?

actually, this is the important question that
we need to understand.
Uh, right now we focus on theunderstanding how this immune
process is going.
After that, or next questionwill be okay, we are.
We can say that this is themicroglia causes.
Why basal ganglia, why they aregoing to basal ganglia.
Is there something?

(55:52):
Is there any relationship withthe basal ganglia?
Against the infection?
If you want, my idea is that Ibelieve some neurons express, uh
, more cytokine receptor thanothers.
So I think that's that's.
That's my thing.
That's my thing.
That and then, and that's whatI'm thinking, but I need to do

(56:14):
really to be certain, I need todo an experiment.
If I can do it.
That's my plan.
It's always in the back of mybrain.
I'm telling myself oh, thiscould be one great project.
Then I can tell you thatexactly, is this or not?

Because I would think you eventually
interested in doing research onthat, given your other interests
, beginning withneuropsychiatric disorders and,
of course, the role of theimmune system and infection.

And then also type of infection.
That's the other thing that Iwould like to do.
For example, why strep?
Why?
Why is not staphylococcusaureus?
Or why not the other pathogen?

well, and what is there?

a strain of strep that is more likely, yeah
why, or are there anyspecificity of the strain, right
or so?
These are the questions that Iwould like to ask in the future.

We've covered a lot of ground here, a lot of
really interesting material here.
What would you like to?
What's your future?
What would you like to continueto work on?

First, I would like to finish my study in here.
Thanks to you right now it'skind of you helped me a lot,
because right now I'm cool, Ifeel relaxed and then I can
fully focus on my project.
First, I would like to finishthis one academically.
I would like to be a, you know,have my own lab and then in my
own lab, I think I would likelike to work on this.

(57:51):
Neuropsychiatric disorders andwhy they're causing.
Is there a peripheral immunerelationship?
And also I would like tocontinue working on the PANDAS
why this is happening, or isthere any specific peripheral
cues that cause these behavioralchanges?

(58:11):
The peripheral cues that causethis behavioral changes or any
specific neurons are morevulnerable compared to other
type of the neurons, or why it'sgas specific.
What is gas doing?
Is there anything that wemissed?
That's all the things that Iwould like to do, but my focus
will be on the blood-brainbarrier, neurobehavioral
diseases, as well as PANDAS andalso the microglia.

(58:33):
I believe these are the thingsthat I would like to continue to
work on it.

Well, we certainly hope that you do
continue to work on it because,as you are learning, pandas and
PANS are really horrificdisorders that need a whole lot
more research.
I mean, we need more cliniciansto diagnose and effectively
treat this disorder, but wereally need more research, the

(58:59):
kind that you are doing and thatDr Aguilillo is doing, and
we're fortunate to have manyother researchers working on
other aspects of this, and Ithink if we continue to get you
all together talking, we canhave a much better idea of
what's going on.

(59:19):
And so this year we have as ourtheme dialogue saves lives,
with the idea that if we bringpeople from different
disciplines together and youtalk, we can make great strides
in understanding PANDAS and PANSand other psychiatric disorders
.
Because, of course, it's notlimited to PANDAS and PANS.

(59:40):
It's, as your work points out,bipolar schizophrenia,
depression.

Yeah, yeah, you are definitely right.

All right.
Well, thank you so much forthis interview.
You leave me, and, I'm sure,the listeners, with lots to
think about, and, following ourinterview, I have an interview
with Dr Agalio to talk about thekind of postdoc that you

(01:00:10):
started out on and the effectsof the funding cuts.
So listeners stay on and we'llpick up with Dr Agilou in just a
few moments, but thank you verymuch again, dr Akcan.

Uğur Akcan, PhD (01:00:23):
Thank you.
Thank you for giving me theopportunity to talk about me
actually and what I'm doing.
And then I need to say thatenglish is not my native
language.
If I made mistake, I'm sorryfor that.
I would like to thank again tothe people who helped me.

(01:00:44):
We will try to show me theirsupport, because I wasn't
realized that your support wasthat kind of big.
Helpful for me just seeing thatyou're especially you, susan,
and also the foundation, theshowing their support.
It's also really helpful toshowing that some people really

(01:01:06):
hearing me what I'm doing,because this is the only problem
, one of the biggest problemwhen you're doing the science.
And then and after I told youthat I started to hearing so
many patients from turkey to tryto reach me out.
I wasn't aware before I startedjoining the agaloy lab, but
right now the people from turkeyjust starting to writing me

(01:01:28):
email or try to reaching out mewe have child children and
thanks for your work.
And then it's really meaningfulfor me.
At least I'm showing that I'mhelping the people from here and
then I'm helping people aroundthe worldwide and thank you for
you.
And then thank you for all ofthe people for their support

(01:01:48):
again, and then thank you.

Dr. Susan Manfull (01:01:52):
It's our pleasure to be in a position
where we can support you becauseyou're doing super work and I
know I speak for the entirecommunity in saying that and we
thank you.

Uğur Akcan, PhD (01:02:02):
Thank you.

Thank you, I think we did it Cool, I hope.
Now you can go have a bigTurkish breakfast.
Yes, my second guest today isDr Dritan Agaliu.
He is an associate professor ofpathology and cell biology at

(01:02:26):
Columbia University and he's thefounder of the Agaliu Lab, a
lab that you've already heardquite a bit about with Dr Akchon
.
Dr Akchon, I asked him if hewould come in today to talk
about how the funding cuts haveaffected his lab and, in

(01:02:47):
particular, how they haveaffected the postdoc position
that Dr Akchon began earlierthis year.
Research in Dr Agalu's lab isfocused on understanding the
cellular and molecularmechanisms that regulate
formation of the blood-brainbarrier in the central nervous

(01:03:09):
system, cns diseases such asstroke and autoimmune diseases
having symptoms that includeblood-brain barrier failure,
which of course includes PANDASand PANS.
He uses a variety of genetic,molecular, cellular and imaging

(01:03:36):
approaches.
In his research.
The lab has developed novelmouse strains that allow the
visualization of changes in thestructural components of the
blood-brain barrier.
So in March of this year, he andother faculty members were

(01:03:57):
notified that NIH funding toColumbia University would be
terminated.
Specifically, $400 million fromvarious federal agencies,
including $20 million in grantsin the medical school, would be
cut.
I've already explained earlier,or I've provided, the

(01:04:19):
explanation that's given by theTrump administration for these
cuts.
They claimed that the protestson campus against Israel's
military campaign in Gaza wereanti-Semitic, and he will
explain more about how they haveaffected his lab.
So, without further ado, let'swelcome Dr Agaliu.

(01:04:42):
All right, welcome, dr Agaliu.
Thanks very much for hopping onto the podcast to answer a few
questions about the funding cutsand how they have affected you
and Dr Akchon's work.
As listeners know, now that DrAkchon's work in your lab has

(01:05:06):
been greatly affected, let'sjust start off with some really
basic information.
He was on a fellowship.
It's a TL1 fellowship.
I'm wondering if you can tellme what kind of a fellowship
that is.

Dritan Agalliu, PhD (01:05:23):
Hello Susan , great to be with you this
morning.
A fellowship from the IrvingInstitute for Clinical and
Translational Research here atColumbia University.

(01:05:46):
This is a training and educationfellowship under a program
called TRANSFORM, which standsfor Training and Nurturing
Scholars for Research.
That is multidisciplinary, andthis is an NIH-funded program
that aims to produce clinicaland translational researchers

(01:06:11):
who are familiar withinterdisciplinary team
structures, comfortable withleadership roles, and they're
able to integrate research fromother disciplines and
pathologies.
So the TRANSFORM program hastwo types of training
fellowships the TL1 fellowshipfor postdoctoral researchers and

(01:06:35):
the TL1 fellowship for graduatestudents.
The goal of both of thesefellowships, and in particular
the one for the post-doctoralresearch scientists, is to train
, to prepare them for a researchcareer that kind of contributes
in a meaningful way tounderstanding risks for disease,

(01:06:56):
improving diagnosis andprevention and tailoring
treatment based on geneticvariation, the role of
environment, the lifestyle andso on.
So Ur applied for thisfellowship about two years ago
and he was awarded it becausehis research, which is focused

(01:07:20):
on understanding the geneticrisk factors for PANS, and PANS
fits very well with the goal ofthe program is really
translational to basicallyunderstand the pathogenesis and

(01:07:42):
the risk of the mechanisms ofthe disease in order to develop
tools for diagnosis andtreatment of children who suffer
from penance and pens.

And as a TL1 fellowship that was terminated.
And so what were theimplications for Dr Akchand?
If you could tell me aboutthose first, and then I
certainly want to know about theimplications for your lab.

So Dr Ak-Chan's stipend, so his salary
, his benefits, as well as someportion of the research, was
funded by this fellowship.
When this fellowship wasterminated in March of 2025, Dr
Ak-Chan lost immediately fundingto support his salary.
Therefore, without this fundingit wasn't you know we were not

(01:08:53):
going to be able to pay DrAk-an's salary, and the
university advised that weterminate his appointment
immediately because of the lossof the funding.
Unfortunately, unlike forgraduate students, for which the
university has a commitment tooversee the students' completion

(01:09:15):
of their training and untilthey receive the degree, this is
not the case for postdoctoralresearch scientists.
Postdoctoral researchscientists are typically hired
on a year-to-year basis fortheir training, with the
understanding that if thefunding for the research is

(01:09:37):
terminated in one way or another, then there is no obligation
for the university to keep thispay loss and they can look for
other positions.

And if they don't find another position
because of course many positionshave been cut during this time
with a TL1 fellowship, would therecipient be required to return
to their native country?

yes, that that is correct, susan.
So you know, particularly forDr Ak, who is a native of Turkey
, of course, the implicationsare quite vast, because with the
termination of this fellowshipprogram in March, he lost the
funding to support his salaryand benefits for him and also

(01:10:35):
for his family he's married witha child.
The second one is, of course,he would be unable to continue
the research, but the mostimportant one is that right now
then he would lose also his J-1Bstatus and would be forced to
return to his home country.
I think that all of thesecreated a significant stressful

(01:11:02):
period for him, particularly inMarch, because all of a sudden
it's a situation where,basically, he would be forced to
return to his country,immediately, forced to return to
his country immediately.

Well, that's tough, very disruptive and very
stressful.
And can you refresh my memory,how long was this fellowship
supposed to be?

So this fellowship, dr Ak chan was
awarded a two-year fellowshipand this fellowship for him
started in september of 2024 andis uh was planned to basically
end in may of 2026 and andtherefore basically dr chan had

(01:11:59):
just completed six years of thisfellowship excuse me, six
months, but this fellowship alsoprovides significant
theoretical training on clinicalresearch so that basically the

(01:12:31):
fellows who complete thisprogram get a broader
understanding of the research atmultiple levels.
They get a better understandingabout the disease.
They also try to understand howclinicians work and basic

(01:12:52):
scientists.
So the goal of this program isreally to build the next
generation of, you know, basicscientists who can integrate
very easy with the clinicalstudies.
And I think the reason thisprogram was developed is that,
because of the number ofphysician scientists is

(01:13:13):
relatively small and a lot ofthe physician scientists who
receive a PhD, most of themchoose to do clinical work, the
goal is to really train thebasic scientists who are
interested in mechanisms ofdisease to get a better
understanding about medicine.
It's a fantastic program and wewere really excited that Dr you

(01:13:39):
know were, you know that DrAchan was awarded this
fellowship because, as we allknow, pandas and pans is
somewhat controversial, so wereally weren't sure that the
university and the program wouldembrace his research.
But you know, I think he wrotea wonderful fellowship and you

(01:14:04):
know he was one of the only fourpeople who received this award
among a large number ofapplicants, so you can
understand how competitive thisfellowship was.

Well, you're doing such cutting edge research
in your lab with the bloodbrain barrier, further
understanding that, especiallywith regard to pandas and pans.
So to lose someone doingresearch in that area is very
upsetting.
And then, as you mentioned, Ithink that there's certainly a

(01:14:40):
shortage of physician scientistsin this area.
So all the way around, this wasreally disappointing.
How and well, and I should saythat earlier in the podcast
we've talked to Dr Akchon abouthis research, in particular the

(01:15:01):
genetic research, the RXRAresearch and the TH17 research,
and we know that your lab hascontributed quite a bit already,
especially in the understandingof the role of TH17 and now
this genetic research.
So what with this sudden and Ido underscore sudden he told us

(01:15:29):
that he walked into a buildingfully employed and when he
walked out of that particularbuilding he was unemployed.
So it was very sudden.
What kind of an effect did thishave on your lab?

So I mean this is very devastating because
currently, in my laboratory, drAk-Chan is the only person who
is conducting research on pantsand pants and so and he is a
very senior research scientist.
So, with the loss of Dr Ak-Chan, this would basically come to,
you know, terminate our researchon potassium-pens for a while,

(01:16:13):
until I am able to find anotherresearch scientist who can
continue this research.
Therefore, even you know,contrary to most people's
beliefs, pis don't really do alot of experiments on a daily
basis.
We are tied up in ouradministrative and research

(01:16:40):
duties, but we don't runexperiments, and so we rely on,
you know, research scientists,postdoctoral research scientists
, graduate students to run theday-to-day experiments.
And therefore, even though I'mone of those few scientists who
still contributes to meaningfulresearch in the lab, obviously

(01:17:01):
the majority of the experimentson pain and less than pain is
conducted by Dr Ak-Chan, and so,therefore, this would be
devastating to Lucy.

Just in general, when you terminate
research midstream before it'scompleted, how does that affect
the research itself?

That definitely slows down the
research.
If we don't have the funding,we have to terminate, you know,
the mouse colony that we use forour research.
As you know, we're one of thefew labs with as basic
translation or research using amouse model for pants and pants

(01:17:55):
right, and therefore we have arelatively large colony of
rodents that we maintain inorder to conduct our studies.
These are either wild-type miceor genetically modified mice

(01:18:17):
that we we have eliminated thegene RxRA in a subset of cells
called the microglial cells,which are the innate immune
cells of the brain.
So therefore, with the endingof the funding, we would also
not be able to support the mousecolony and we'd need to

(01:18:41):
terminate those Now.
This is extremely expensivebecause it takes roughly about
two years to generate thecorrect or the mice that have
the correct genotype, thecorrect combination of genes
that you need for the research,a combination of genes that we
need for the research and, if wehave to, if we're forced to

(01:19:03):
terminate these, I think thatbasically we'll have to start
this from the beginning, sowe'll lose several years of
research.
In some cases we can, we can.
You know, we have some of thebrains we have collected from
them frozen down, but obviouslyfor a lot of future experiments.

(01:19:27):
So we don't be able to continueand usually the research
process works such as that onceyou prepare a publication, you
submit it for a process calledthe peer review and during the
peer review the reviewers maycome back and ask for more

(01:19:48):
experiments, for which you mayneed to generate more and more
mice.
Therefore, you know, thisprocess, you know, doesn't end
with you completing the set ofstudies that you think are
important.
You have to address thereviewers' concerns, which means
that we have to probably keepthese mice going until the paper
is fully published andtherefore it's tricky to like

(01:20:14):
terminate the mice even when youthink the work is done, because
you never know what thereviewers are going to ask you
to complete the study.
In my case, we keep a lot ofmice for the projects that are
completed, but the papers arestill in the review, revision
process until the paper is fullypublished.

(01:20:36):
Only when the paper is fullypublished then we can, of course
, move on and talk about how wemade those mice.
But you know this is anextremely expensive enterprise
and I think, just to give you asense, the typical mouse costs
for the research that I conductin my laboratory are about

(01:20:57):
around about six thousand toeight thousand dollars per month
, um, so, um, you know, in ayear we're talking about, you
know, a significant amount ofmoney, seventy two thousand and
dollars per year to just supportof the uh cost for maintaining

(01:21:18):
and preheating the, of the costfor maintaining and preheating
the mouse colony, withoutdiscussing at all other reagents
that we may need, of course, tocomplete the experiments that
we need for the study.
And some of these experiments,particularly those that involve
the sequencing of the RNA,involve the sequencing of the

(01:21:39):
RNA to understand how the geneschange in the brain.

Those are also extremely expensive.
I don't think that that'ssomething that the average
person thinks about.
I think when we all read thatDr Akchon's position had been
terminated, we thought about him, we thought about your research
in general and therefore you,but I don't think the average

(01:22:07):
person really thinks about theimplications beyond that.

That is the mice, a lot of mice, but of
course we need those.
I mean, you know, that's why wedo this research, because, as
you know, it's impossible to dothis type of work in humans.

Yes, yeah, the mice are and how important

(01:22:48):
they are in this particular, howintegral to your research these
mice are.
So you have been able to keepDr Akchon on because you
immediately began to raise fundson his behalf.
There are a number ofnonprofits who have contributed
to his salary the Alex ManfieldFund, did I know Panda's Network

(01:23:12):
, did Northwest Panda's Network,sarah Lemley's group and
Panda's Physicians Network andthe Look.

Foundation.
We had just another majordonation come from Mike and
Priya for about $23,000 justyesterday.
So these are, you know, thePANDAS Physician Network, pandas
Network, all the Manful, theAlex Manful Foundation, the

(01:23:51):
Northwinds PANDAS PANS Networkand obviously I think these were
the major donors.
Yeah, but lots of individualdonors and I think one, one
person, one individual donor.
That I think was was reallyimpressive.
We just received, actually onjune 17, uh, some funding for

(01:24:12):
two thousand five hundreddollars for word from a high
school, the cla Clausen Schoolin Michigan, and there was a
high school kid, raymondLangfier, who really had
suffered from PANS.
He's recovered and he reallydid a lot of work to do a lot of
fundraising in his classroomand was able to raise $2,500 for

(01:24:37):
the research.
So you can understand how thishas resonated with a lot of
people, because obviously thereis a lot of people who are
affected by the disease and I'mvery impressed to see that they
really understand and appreciatethe amount of work that we're

(01:24:59):
doing for this disease.

If some of our listeners would like to
contribute.
You have a GoFundMe and we willput that information.
We will put a link to theGoFundMe on our podcast episode
description page on our websiteand also you'll be able to read
it wherever you get yourpodcasts.

(01:25:24):
But is it something that youcould tell us right now where
they could go?

Yes, so the Columbia University Department
of Neurology Advancement Officehas created a your Columbia Gov
and Me, so it's a and basicallyit's.
The website is ACPPS, join uscoimccolumbiaedu.

(01:25:53):
And obviously in this it tellsyou a little bit about the story
of Dr Ak-Chan, how he you knowhis training and also his work
on PANS and PANS research.
And there is also a donationthat is directly linked to the

(01:26:17):
funding that we use for PAMS andPAMS research.
So we set a goal for $100,000.
This will be able to support DrAk-Chan's salary, as well as
his benefits for one year, whichwould allow him to complete the
study and submit it forpublication, and also this will

(01:26:38):
give Dr Ak-Chan opportunity toapply for our faculty positions.
And so far we've been able toraise about 84,000.
We still have about 16,000 moreto go, but I'm really excited
to see how community has cometogether.

(01:26:59):
So I wanted to thank everyonein particular.
I wanted to also thank the AlexManfield for supporting Dr
Akhchan and this endeavor,because without you, we would
lose Dr Akhchan and we would notbe able to continue the
research.

Thank you for that and we don't want you to
lose him and we want you to beable to continue your absolutely
excellent research that'scontributed in many ways to
understanding the symptoms, thethe symptoms, how the symptoms

(01:27:50):
emerge in the case of pandas andpans.
So In In, in thinking a littlebeyond your lab.
Your Columbia has lost thisfunding, other schools have lost
the funding and, most likely,other universities will be

(01:28:10):
affected.
Is there any advice that youwould give to researchers who
may find themselves in a similarsituation?

who may find themselves in a similar
situation.
So one thing that I think theevents in March have triggered
is a sort of awakening in a lotof academic institutions.
We obviously rely heavily onfederal funding from the
National Institute of Health,the National Science Foundation

(01:28:40):
for the research.
However, the change in thefunding landscape has created
this bigger awareness that weshould also rely on smaller
donations and I think, eventhough you know, in the past the
universities have dissuaded alot of scientists from applying

(01:29:03):
for small foundation fundsbecause these small foundation
funds don't provide a lot ofindirect costs, I think right
now all the universities arebecoming aware that this is a
very good way to sustain theresearch, probably not at the
level of the federal funding,but I think it will allow us to

(01:29:29):
move forward in these difficultand challenging times.

Well, we've certainly recognized that and
are endeavoring to raise moremoney for exactly cases like
yours.
Well, I think that about wrapsup our conversation.
Is there anything that you'dlike to add that I neglected to

(01:29:58):
ask?

So I also just want to say that I think,
with the current researchlandscape, I think it's also
important for everyone toconsider different avenues for
how we can act.

(01:30:21):
Research, and I think one ofthe ways in which we need to be
a little bit more aware asscientists is, you know, to be
able to disseminate our findingsmore broadly to the public,
because one thing that hasbecome very clear is the public
doesn't fully understand whatyou know, what we do as

(01:30:44):
scientists, and how difficultsometimes the research that we
do is to basically come to ourunderstanding of the mechanisms
of disease and to the pamphlettreatments, and I think it falls
upon us to do that.
I've been a very strongadvocate about, you know,

(01:31:10):
meeting with parents andadvocacy groups to tell them
about our research on pentapsand pants, but I think that
right now I think this isbecoming more and more important
that we need to do in thefuture.

That is such a good point.
I completely agree with youthat the average person doesn't
understand the role of researchin eventually shortening the
period of time between the benchand the bedside, and that's the
bottom line.
We want to understand theunderlying mechanisms of, in

(01:31:42):
this case, pandas and pans, butwe also want to be able to
improve diagnosis, treatment andactually hasten the ability,
ability to diagnose.
So because the earlierindividuals are diagnosed, the

(01:32:03):
better the the prognosis iscertainly.
I think that's really soimportant and, um, I will
definitely tuck that away andsee what we can do towards that.
The podcast, I think, helps umin getting the information out
there, but there are um, thereare other ways as well.

Thank you for for bringing that up and
thank you for all the workyou're doing with the podcast
because that definitely helps alot in disseminating the
information and I think a lot ofthe non-profit organizations
should really make an effort tolike invite basic and clinician
science is to really disseminatetheir research or the clinical

(01:32:46):
endings to the other public.

I do too, and it's very interesting I mean,
it's very interesting to talk topeople like you.
What drives you?
How did you get into this?
What do you want to accomplish?
What's most meaningful to you?
All of those things.
That information about theresearcher is also interesting
to the average person, as wellas their findings.

(01:33:12):
So we'll We'll endeavor tocontinue to do that.
Thank you very much.
Thank you very, very, very much, dutton, for agreeing to talk
with me today.

Thank you so much, Susan.
Thank you for inviting me.

Thank you for coming, all right.

William Manfull (01:33:37):
Thank you.
This concludes Episode 15 ofUntangling Pandas and Pans.
Thank you for listening.
For more information aboutPandas and Pans and the Alex
Manful Fund, please visitthealexmanfulfundorg.

(01:34:00):
The content in this podcast isnot a substitute for
professional medical advice,diagnosis or treatment.
Always seek the advice of yourphysician or other qualified
healthcare provider with anyquestions you may have regarding

(01:34:21):
a medical condition.

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